As­traZeneca’s big MYS­TIC tri­al ends a com­plete fail­ure as Imfinzi/treme­li­mum­ab com­bo flops on over­all sur­vival

Last year, As­traZeneca preached pa­tience af­ter ini­tial da­ta showed its check­point in­hibitor Imfinzi com­bined with their in-house CT­LA-4 drug failed to meet the pri­ma­ry end­point of pro­gres­sion-free sur­vival in a piv­otal lung can­cer tri­al. On Fri­day, that faith proved in vain as the im­munother­a­py al­so failed to im­prove over­all sur­vival in the keen­ly watched MYS­TIC tri­al.

The tri­al test­ed Imfinzi both as a monother­a­py and in com­bi­na­tion with an­oth­er check­point in­hibitor, treme­li­mum­ab, against chemother­a­py in treat­ment-naive pa­tients with stage IV non-small cell lung can­cer (NSCLC), a cru­cial are­na in the bat­tle for check­point drug dom­i­nance.

The phar­ma gi­ant $AZN con­ced­ed Fri­day morn­ing that the com­bi­na­tion — once con­sid­ered a cor­ner­stone of As­traZeneca’s check­point de­vel­op­ment strat­e­gy — ac­tu­al­ly per­formed worse than Imfinzi alone for the over­all sur­vival end­point, with a haz­ard ra­tio of 0.76 for the so­lo drug com­pared to an ane­mic 0.85 for the two to­geth­er.

Sean Bo­hen

While As­traZeneca’s pipeline has of­ten come up short, there have been a string of ma­jor suc­cess­es in on­col­o­gy for the com­pa­ny. This tri­al was con­sid­ered crit­i­cal in putting the brakes on the blitz­ing gains Mer­ck $MRK and Bris­tol-My­ers Squibb have made af­ter es­tab­lish­ing their lead in the lu­cra­tive front­line can­cer field. The study was al­so tout­ed by CEO Pas­cal So­ri­ot as an in­di­ca­tor of the British drug­mak­er’s val­ue as an in­de­pen­dent en­ti­ty, when it spurned Pfiz­er’s $PFE $118 bil­lion takeover bid in 2014

In a state­ment on Fri­day, As­traZeneca al­so sug­gest­ed that al­though sta­tis­ti­cal sig­nif­i­cance for over­all sur­vival had not been met, the da­ta mer­it­ed fur­ther analy­sis in ex­plorato­ry sub­groups. That’s not like­ly go­ing to in­spire much en­thu­si­asm.

Brad Lon­car

In MYS­TIC, “CT­LA-4 tru­ly of­fered no ben­e­fit or sig­nal at all”, said Brad Lon­car, man­ag­er of the Lon­car Can­cer Im­munother­a­py ETF. “I would think hard about these re­sults if I was one of the com­pa­nies out there de­vel­op­ing me-too or me-bet­ter CT­LA-4s (of which there are many). Giv­en its tox­i­c­i­ty pro­file and now the emerg­ing com­bo ef­fi­ca­cy we are see­ing in some of these can­cers out­side of melanoma, its win­dow is look­ing quite nar­row.”

As­traZeneca’s shares were al­so un­der pres­sure again on the fail­ure. Its stock is down more than 3% in pre-mar­ket trad­ing. Shares fell sharply last year on the PFS miss, evap­o­rat­ing some $14 bil­lion off the com­pa­ny’s val­ue.

Since that ini­tial set­back on MYS­TIC, though, As­traZeneca scored a big win with its PA­CIF­IC tri­al for Imfinzi, win­ning a sig­nif­i­cant mar­ket niche for it­self in stage III NSCLC. But the fail­ure here will sting, nev­er­the­less.

Chief med­ical of­fi­cer Sean Bo­hen spot­light­ed the suc­cess on the monother­a­py side, but con­ced­ed the key fail­ure:

We are en­cour­aged to see that Imfinzi monother­a­py ac­tiv­i­ty is in-line with that of the an­ti-PD-1 class in pre­vi­ous­ly-un­treat­ed pa­tients with Stage IV non-small cell lung can­cer; how­ev­er, we are dis­ap­point­ed that these re­sults missed sta­tis­ti­cal sig­nif­i­cance. We re­main con­fi­dent in Imfinzi as the cor­ner­stone of our IO pro­gramme and con­tin­ue to eval­u­ate its po­ten­tial in on­go­ing non-small cell lung can­cer tri­als, in­clud­ing Imfinzi and Imfinzi plus treme­li­mum­ab in com­bi­na­tion with chemother­a­py.


Im­age: Pas­cal So­ri­ot. AP IM­AGES

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.

J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.